B4.017 Prework 3 Treatment of Cardiac Arrhythmias Flashcards
2 main classes of drugs used to treat arrhythmias
rate control agents
rhythm control agents
rate control agent classes
b-blockers (metoprolol, atenolol)
Ca2+ channel blockers (verapamil, diltiazem)
digoxin
rhythm control agents
Na+ channel blockers (Procainamide, quinidine, disopyramide, flecainide, propafenone)
K+ channel blockers (amiodarone, ibutilide, sotalol, dofetilide)
Class I overview
Na+ channel blockers
decrease HR by:
-elevating threshold for excitation
-decreasing slope of phase 4 depol in SA node
Class II overview
B blockers
-decrease HR
Class III overview
K+ channel blockers
-prolong AP duration and refractory period
Class IV overview
Ca2+ channel blockers
-decrease conduction velocity
Class IA overview
moderate Na+ channel block
dissociate with intermediate kinetics
prolong AP duration
also inhibit K+ channels
Class IB overview
mild Na+ channel block
fast dissociation
shorten AP duration
shortened repolarization
Class IC overview
strong Na+ channel block
slow dissociation
minimal effects on AP duration
no change in repolarization
members of Class IA
procainamide
quinidine
dispyramide
members of Class IB
lidocaine
mexiletine
members of class IC
flecainide
propafenone
moricizine
procainamide cardiac effects
increases effective refractory period of the atria and ventricles
can directly depress SA and AV nodes
prolongs AP duration by nonspecific blocking K+ channels
procainamide extracardiac effects
has ganglion blocking activity
reduced peripheral vascular resistance can lead to hypotension
procainamide toxicity
cardiotoxic: excessive AP prolongation, QT prolongation, induction of torsades de pointes, arrhythmia and syncope
long term: reversible lupus like syndrome (rash, arthralgia, arthritis, pericarditis)
other: nausea/diarrhea, rash, fever, hepatitis, agranulocytosis
procainamide therapeutic use
effective against most atrial and ventricular arrhythmias
short half life (3-4 hrs): oral dosing every 6 hours
less useful for long term (shoft half life and adverse effects)
2nd or 3rd choice for sustained ventricular arrhythmias associated w MI
quinidine cardiac effects
slows upstroke of action potential
slows conduction
QT prolongation due to K+ channel blocking
modest antimuscarinic effect
quinidine extracardiac effects
blocks a-adrenergic receptors to cause vasodilation
-hypotension and reflex tachycardia
quinidine toxicity
increase plasma digoxin precipitate digoxin toxicity thrombocytopenia syncope (due to torsades de pointes) adverse GI effects (30-50%), cinchonism
quinidine therapeutic use
rarely used
better tolerated drugs available
disopyramide cardiac effects
similar to quinidine and procainamide but more antimuscarinic effects (tend to accelerate HR)
disopyramide toxicity
adverse effects caused by its pronounced atropine like activity
- urinary retention
- dry mouth, blurred vision, constipation
- worsening of preexisting glaucoma
disopyramide therapeutic use
not used often bc of antimuscarinic effect
not first line bc negative inotropic action may induce CHF
ventricular arrhythmias only**
similarities between class IA antiarrhythmics
all block Na+, K+ channels, and can induce torsade de pointes
lidocaine administration
must be given IV
high first pass hepatic metabolism (only 3% in plasma)
lidocaine therapeutic use
ventricular arrhythmias associated with MI or digoxin toxicity
relatively ineffective in normally polarized tissues as in atrial flutter or fibrillation cardiac events
lidocaine toxicity
low incidence of toxicity and high degree of effectiveness
mexiletine administration
lidocaine analog, resistant to first pass hepatic effect so effective orally
mexiletine uses
electrophysiologic and antiarrythmic actions like lidocaine
useful for ventricular arrhythmias
relief of chronic pain, esp diabetic neuropathy and nerve injury (off label)
mexiletine adverse effects
predominantly neurologic
tremor, blurred vision, lethargy, nausea
similarities of all Class IC drugs
all oral
increase mortality from cardiac arrest or arrhythmic rudden death in pts with recent MI
flecainide mechanism
blocks Na+ and K+ channels, no QT prolongation
no antimuscarinic effects
flecainide therapeutic use
supraventricular arrhythmias
very effective in suppressing premature ventricular contractions
propafenone mechism
blocks Na+ channels
structurally similar to propranolol, thus weakly B blocking activity
propafenone adverse effects
metallic taste
may exacerbate arrhythmias and cause constipation
propafenone therapeutic use
supraventricular arrhythmias
very effective in suppressing premature ventricular contractions
(same as flecainide)
moricizine mechanism
potent Na+ channel blocker that does not prolong action potential
moricizine therapeutic uses
was used for ventricular arrhythmias
withdrawn from US market
propranolol (nonselective) and atenolol (b1) therapeutic uses
rate control
supraventricular and ventricular arrhythmias caused by SYM stim
prevent v-fib
esmolol (b1) therapeutic use
acute tachycardias occurring during surgery
beneficial effects of b blockers
diminished SYM activation of heart and blood vessels
decreased cardiac workload
harmful effects of b blockers
negative inotropy
may induce or worsen HF in patients w acute MI
amiodarone therapeutic use
oral or IV
maintain normal sinus rhythm in patients with a-fib
prevent recurrent ventricular tachycardia
amiodarone cardiac effects
prolongs AP duration (and QT interval) by blocking K+ channels
decreases rate of firing in pacemaker cells by blocking Na+ channels
blocks a and b adrenergic receptors and Ca2+ channels and this inhibits AV node conduction to produce bradycardia
amiodarone extracardiac effects
peripheral vasodilation, esp after IV admin
amiodarone toxicity
aymptomatic bradycardia and AV block in pts with AV/SA node disease
resp difficulties leading to fatal pulm fibrosis (1%)
abnormal liver function and hepatitis
skin deposits (grayish blue skin)
after a few weeks in essentially all pts: corneal microdeposits, reduced visual activity, optic neuritis, can progress to blindness
blocks thyroid function T4 to T3, can result in hyper or hypothyroidism
amiodarone pharmacokinetics
long half life
rapid 3-10 days (50% of drug)
slow for several weeks> toxicity long after its discontinues
amiodarone metabolism
CYP3A4
drug drug interactions
dronedarone mechanism
structural analog of amiodarone without iodine
blocks several K+ and Na+ channels
dronedarone adverse effects
no thyroid or pulm toxicity
liver toxicity
black box warning of increased death, stroke, a d heart failure in pts with decompensated heart failure and permanent a-fib
sotalol mechanism
nonselective b adrenergic blocker that also prolongs AP duration and has antiarrhythmic properties
may cause prolonged repol resulting in torsade de pointes (6% at highest dose)
sotalol therapeutic use
life threatening ventricular arrhythmias
maintaining sinus in a-fib
treatment of supraventricular and ventricular arrhythmias in pediatrics
dofetilide (oral) and ibutilide (IV) mechanism
block rapid component of the delayed rectifier K+ current to slow cardiac repolarization
dofetilide (oral) and ibutilide (IV) therapeutic use
restore normal sinus rhythm in a-fib or flutter
dofetilide (oral) and ibutilide (IV) adverse effects
prolonged QT and torsade de pointes in 10% of pts
verapamil and diltiazem mechanism
orally active block L type Ca channels in myocardium and vascular smooth muscle depress SA/AV nodes directly to: -decrease contractility -reduce SA not automaticity -slow AV node conduction
verapamil and diltiazem therapeutic use
supraventricular arrhythmias
rate control in a-fib
adenosine mechanism
opens inward rectifier K+ channels> hyperpolarization
inhibits L-type Ca channels > inhibits Ca entry and conduction CV in AV node
inhibits pacemaker current > decreases HR
mainly affects AV > SA
adenosine therapeutic uses
IV injection
converts paroxysmal supraventricular tachycardia to sinus
highly efficient (90-95%)
very short half life
adenosine adverse effects
flushing SOB chest burning headache hypotension nausea paresthesia
digoxin mechanism
potent and selective inhibitor of NA+/K+ ATPase > increased Ca2+ > positive inotrope
stimulated vagus nerve and thus decreases HR
digoxin therapeutic use
can be used in a-fib to decrease rate
narrow window
other antiarrhythmic drugs enhance toxicity
many antibiotics increase digoxin absorption
drugs that produce hypokalemia will enhance toxicity (K+ is a competitor)
digoxin toxicity
GI: nausea, vomiting, diarrhea, ab discomfort
cardiac: almost all arrhythmias
magnesium therapeutic use
mag chloride or sulfate (parenteral)
mechanism unknown
prevent torsade de pointes
used against digoxin induced arrhythmias
